The overexpression of 14-3-3ζ and Hsp27 promotes non–small cell lung cancer progression

Authors

  • Guang-Yin Zhao MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
    • The first 3 authors contributed equally to this work.

  • Jian-Yong Ding MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
    • The first 3 authors contributed equally to this work.

  • Jie Gu MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
    • The first 3 authors contributed equally to this work.

  • Chun-Lai Lu MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
  • Zong-Wu Lin MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
  • Jing Guo MD,

    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    Search for more papers by this author
  • Di Ge MD

    Corresponding author
    1. Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China
    • Corresponding author: Di Ge, MD, Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China, 200032, Fax: (011) 86-21-64038472; gedi6902@hotmail.com

    Search for more papers by this author

Abstract

BACKGROUND

The 14-3-3ζ protein has been identified as a putative oncoprotein in several cancers, including non–small cell lung cancer (NSCLC). However, the mechanisms underlying its functions have not been well defined.

METHODS

Proteins that interact with 14-3-3ζ were identified through coimmunoprecipitation and mass spectrometry in NSCLC cells. The interaction of 14-3-3ζ with these molecular partners and their roles in the invasiveness and metastasis of NSCLC cells were assayed through specific disruptions in the 14-3-3ζ signaling network. In addition, the clinical implications of this 14-3-3ζ complex were examined in samples from patients with NSCLC.

RESULTS

Among the identified proteins that interacted with 14-3-3ζ, there were 230 proteins in 95-D cells, 181 proteins in 95-C cells, and 203 proteins in A549 cells; and 16 interacting proteins were identified that overlapped between all cell lines. Further studies revealed 14-3-3ζ complexes within the heat shock protein 27 (Hsp27) protein and demonstrated that the interference of Hsp27 or 14-3-3ζ inhibited the invasion and metastasis of NSCLC cells. The invasive and metastatic capabilities of cells with both Hsp27 and 14-3-3ζ interference could be completely restored only by Hsp27 and 14-3-3ζ complementary DNA transfection and not by either agent alone. Clinically, the postoperative 5-year overall survival (OS) in patients who had high expression of both 14-3-3ζ and Hsp27 was significantly lower than the 5-year OS in patients who had low expression of both 14-3-3ζ and Hsp27 (26.5% vs 59.7%, respectively). Multivariate analysis revealed that the combined expression of 14-3-3ζ and Hsp27 was an independent prognostic indicator of OS (P = .036).

CONCLUSIONS

The current data suggest that the combined expression of 14-3-3ζ and Hsp27 may be a biomarker for predicting survival in patients with NSCLC, and this combination may have potential as a therapeutic target for NSCLC. Cancer 2014;120:652–663. © 2013 American Cancer Society.

Ancillary